PROJECT SUMMARY TESTING CORE The goal of this section is to develop a flexible and scalable murine genome editing testing platform to support the needs of the Jackson Laboratory Genome Editing Mouse Testing Center (JAX-GEMTC) and the Somatic Cell Genome Editing (SCGE) consortium. Our proposed TESTING CORE leverages two existing programs at JAX, the In Vivo Pharmacology Service and the Knock Out Mouse Phenotyping Program (KOMP2)?both of which are expert in high-throughput generation and evaluation of mutant animals?as well as in-house expertise in specific organ systems for the delivery and assessment of genome edit tools to those tissues. We will achieve the goals of this TESTING CORE through the successful execution of the following aims. 1) To establish and implement an in vivo platform for the evaluation of new editing machinery delivery technologies. In this Aim we will apply the techniques, processes and expertise from our In Vivo Pharmacology Service to serve as a robust platform for the delivery of editing components to mouse tissues. We will augment this platform with additional areas of expertise from JAX scientists, including the eye, ear, and heart. 2) To implement an in situ analysis pipeline to characterize reporter activation at the single cell level following delivery of editing machinery. We will leverage our KOMP2 and Cre driver in situ gene expression analysis pipeline, adapting it to support the analysis of fluorescent protein expression. In addition to broad-based analysis of reporter activation at the single cell level, we will provide additional analysis expertise for specific tissues of interest. We will adapt and implement existing KOMP2 data management systems to share all results with the SCGE Data Coordination Center. 3) To generate baseline functional data and establish SOPs for in vivo delivery, analysis of outcomes, and safety and toxicology assessment of new editing delivery platforms. We will apply standard viral delivery systems for credentialing our novel reporter models and to provide a comparative baseline for the evaluation of new delivery technologies. Then, from these outcomes we will generate SOPs for all elements of our process and provide them to the SCGE data coordination center. We will develop additional SOPs for molecular evaluation of editing efficiency in WT/non-reporter mouse cells. 4) To develop a capacity and cost model to support the testing needs of, and future collaborative arrangements with, SCGE members. To accomplish this Aim we will develop a cost model for our overall testing pipeline in close coordination with SCGE members based on their goals and needs to estimate capacity, and to provide a budgetary framework for future collaborative projects. We will also provide detailed descriptions of our resources and capabilities that can support expanded collaborative opportunities.